Novel AP-1 binding site created by DNA-methylation

Eugene M. Tulchinsky, Georgii P. Georgiev, Eugene M. Lukanidin

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

DNA-methylation is known to repress transcription either by inactivation of positive regulatory cis-elements containing CpG dinucleotides or via the sequence-nonspecific and methylation-specific binding of inhibiting methyl-CpG binding protein 1 (MeCP1). In the present work we describe the novel way DNA-methylation can influence gene expression: a binding site for transcription factors AP-1 might be created by DNA-methylation. Such a DNA-methylation-dependent AP-1 binding site was found in the first intron of the metastasis-associated mts1 gene. The expression level of this gene correlates with the hypomethylation of the mts1 first intron sequence in mouse adenocarcinoma cells. The DNA methylation-dependent AP-1 binding site was found to be functionally active in the nucleotide context of the mts1 gene. When methylated, this site reproducibly repressed transcription of CAT-containing DNA that had been transiently transfected into mouse adenocarcinoma CSML100 cells.

Original languageEnglish
Pages (from-to)1737-1745
Number of pages9
JournalOncogene
Volume12
Issue number8
Publication statusPublished - May 24 1996
Externally publishedYes

Keywords

  • AP-1
  • DNA-methylation
  • Gene expression
  • mts1 gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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